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Biomedical subjects

A Gasbarrini

Publications and source records attributed to A Gasbarrini.

At least 181 records · Page 10Linked to original sources

Neoadjuvant chemotherapy for osseous malignant fibrous histiocytoma of the extremity: results in 18 cases and comparison with 112 contemporary osteosarcoma patients treated with the same chemotherapy regimen.

Eighteen patients with high grade malignant fibrous histiocytoma (MFH) of bone and 112 patients with high grade osteosarcoma (OS) of the extremity were treated with neoadjuvant chemotherapy comprised of methotrexate, cisplatinum, doxorubicin and ifosfamide. For the 18 patients with MFH, surgery involved amputation in 2 cases and limb salvage in 16 (89%); the 112 osteosarcoma patients had amputation in 8 cases and limb salvage procedure in 104 cases (93%). The rate of good histologic response to preoperative chemotherapy (90% or more tumor necrosis) was significantly higher in patients with osteosarcoma than in patients with MFH (74% vs 28%; p < 0.003). However, at a median follow-up of 38 months (range 25-61), the 3-year event-free survival (EFS) did not differ in the two groups (MFH 77.8%, OS 70.5%; p = ns). In patients with MFH, no local recurrences were registered, whereas in the osteosarcoma group there were 6 local relapses (5.%). The effectiveness of neoadjuvant chemotherapy in the treatment of osteosarcoma has been assessed during the last 15 years. The results of the present study seem to indicate that, in spite of a usually poor histologic response to preoperative treatment, neoadjuvant chemotherapy is very effective also in MFH of bone.

Adolescent↗

Clinical and pathologic features of hepatocellular carcinoma in young and older Italian patients.

BACKGROUND: It is not known whether putative etiologic factors and clinical and pathological features of hepatocellular carcinoma (HCC) differ between young adult and older white patients. METHODS: We examined the characteristics of 498 consecutive patients with HCC age < 50 years (Group 1: 54 patients) and age > or = 50 (Group 2: 444 patients), an age beyond which the tumor occurrence rate briskly increases. RESULTS: Demographic characteristics, alcohol and coffee intake, and cigarette smoking did not differ between the two groups. Group 1 had a greater prevalence of the hepatitis B surface antigen (HBsAg) carriers (P = 0.006), while the prevalence of either past hepatitis B virus infection (P = 0.008) or antivirus C antibodies (P = 0.016) was higher in Group 2. The lack of both hepatitis B and C virus serologic markers was more common in Group 1 (P = 0.018). In these patients, HCC was less frequently superimposed on cirrhosis (P = 0.002) and was more advanced at the time of diagnosis. In fact, despite a better histologic differentiation grade (P = 0.019), monofocal (solitary and massive) tumors were larger (P = 0.012), small lesions (< or = 5 cm) less frequent (P = 0.028), and either diffuse (P < 0.001) or massive (P = 0.011) types more common. An elevation of serum alpha-fetoprotein was less frequent in group 1 (P = 0.016), but this difference disappeared when the "diagnostic" cut-off of 400 ng/mL was considered. Albeit the prevalence of presenting symptoms did not significantly differ between the two groups, the clinical stage was more advanced in young patients (P = 0.004). The 9-year cumulative rate of survival was similar in the 2 groups. CONCLUSIONS: An early exposure to the virus and/or an accelerated hepatocarcinogenesis in HBsAg carriers can be inferred. Moreover, in the period of life at low risk for hepatoma: (1) the impact of nonalcoholic chemical carcinogenesis seems to be greater; (2) the tumor occurrence is less dependent on cirrhosis development; (3) although histologically better differentiated, the neoplasm is more advanced at the time of diagnosis; and (4) the long term survival is similar to that of the patients age 50 years or older.

Adolescent↗

Effect of ethanol on adenosine triphosphate, cytosolic free calcium, and cell injury in rat hepatocytes. Time course and effect of nutritional status.

The events implicated in the early phases of acute ethanol-induced hepatocyte injury and their relation with the nutritional status of the liver are not clearly defined. We aimed to determine the effect of ethanol on ATP and cytosolic free Ca2+ in hepatocytes isolated from fed or fasted rats. Cell injury was assessed by LDH release and trypan blue uptake, ATP by [31P]NMR spectroscopy, and cytosolic free Ca2+ with aequorin. In control conditions, cells from fasted animals had a lower ATP level (-52%) and a higher cytosolic free Ca2+ (+101%) than did those isolated from fed animals. Ethanol caused a dose-dependent cell injury in both groups. At all ethanol doses, greater, damage occurred when using hepatocytes isolated from fasted rats. In both groups, a dose-dependent decrease in ATP content and a rise in cytosolic free Ca2+ were seen. The magnitude of these changes were significantly greater in the fasted group. In conclusion, these data showed that fasting affects the energy status and cytosolic free calcium level in hepatocytes; ethanol causes a dose-dependent cell injury that occurs in association with a fall in ATP and a rise in cytosolic free Ca2+ levels. The nutritional status of an animals is an important determinant of the severity of ethanol-induced damage to liver cells.

Adenosine Triphosphate↗

Biochemical and 31P-NMR spectroscopic evaluation of immobilized perfused rat Sertoli cells.

Cell immobilization and perfusion are used for physiologic studies of Sertoli cells with phosphorus 31 nuclear magnetic resonance (NMR) spectroscopy and biochemical methods. In this study the 31P NMR spectra of Sertoli cells isolated from 18-to 21-day-old rats and immobilized in agarose threads continuously perfused with oxygenated Dulbecco's modifed Eagle medium were obtained at 81 MHz on an NMR system. Cytosolic Ca2+, intracellular Mg2+, lactate and pyruvate, and oxygen consumption were measured with standard biochemical methods. Perfused Sertoli cells maintain a stable intracellular adenosine triphosphate concentration for more than 10 hours. Sertoli cells placed in cold storage overnight and then subjected to perfusion partially regenerate cellular adenosine triphosphate levels. Sertoli cells consume an average of 4.8 +/- 0.4 nmol O2/min/10(6) cells and maintain average ambient lactate and pyruvate levels of 7.1 +/- 0.8 mg/dl and 0.65 +/- 0.05 mg/dl, respectively, with a lactate/pyruvate ratio in the range 8 to 12. The basal Ca2+(i) of Sertoli cells is 98 +/- 0.7 nmol/L (n = 58), which declines to a level less than 10 nmol/L when the Sertoli cells are perfused with a calcium-free medium. Perfusion of Sertoli cells with a sodium-free medium, with 10(-6) mol/L carbonyl cyanide P-trifluoromethoxy-thenylhydrozone, or with Ca2+ ionophore A23187 at a concentration of 10(-6) mol/L increases the Ca2+(i) to a level of 426 +/- 107 nmol/L, 274 +/- 29 nmol/L, or 282 +/- 57 nmol/L, respectively. A bioreactor for physiologic studies of Sertoli cells in real time with NMR spectroscopy has been developed. These data demonstrate that isolated, immobilized, and perfused Sertoli cells are stable for prolonged periods. In addition, these data suggest that Sertoli cells possess a functional Na+-Ca2+ antiporter and that they sequester extracellular Ca2+ in one or more intracellular compartments.

Animals↗

Plasma endothelin-1 and -3 in cirrhosis: relationship with systemic hemodynamics, renal function and neurohumoral systems.

BACKGROUND/AIMS: The postural change from upright to supine is a physiological maneuvre which increases central blood volume. This model was used to investigate the effects of changes in effective volemia on plasma endothelin-1 and -3 concentrations in cirrhosis. METHODS: Plasma endothelin concentrations, measured by radio-immunoassay, were determined in 20 patients with cirrhosis, 10 of whom has ascites, and nine healthy control subjects, in the upright posture and 30, 60 and 120 min after the assumption of the supine position. RESULTS: In the upright posture, endothelin-1 was 8.9 +/- 0.4 pg/ml and endothelin-3 3.7 +/- 0.6 (mean +/- SEM) pg/ml in control subjects. Endothelin-1 was increased only in patients with ascites (12.7 +/- 1.4 pg/ml, p < 0.05; patients without ascites: 9.7 +/- 0.7 pg/ml), while endothelin-3 was elevated in both patients with and without ascites (8.0 +/- 1.5 pg/ml, p < 0.01; 5.9 +/- 0.5 pg/ml, p = 0.01, respectively). In the supine position, no significant changes in endothelin-1 or -3 occurred either in patients with ascites or in controls throughout the observation period, while a reduction in endothelin-3 was found in compensated patients after 30 and 60 min. In patients, we found negative correlations between endothelin-3, but not endothelin-1, and mean arterial pressure, both in upright (r = -0.59; p < 0.01) and supine (r = -0.56; p = 0.01) positions, atrial natriuretic factor (r = 0.50; p < 0.05) and plasma renin activity (r = 0.67; p = 0.001) in the supine position alone. In patients with ascites, endothelin-1 was inversely correlated with both glomerular filtration rate (upright: r = -0.62; p = 0.06; supine: r = -0.71, p < 0.05) and renal sodium excretion (upright: r = -0.82; p < 0.01; supine: r = -0.88; p < 0.001). CONCLUSIONS: Plasma endothelin-1 and -3 were increased in cirrhosis with ascites, while, in pre-ascitic cirrhosis, only endothelin-3 was increased in the upright posture. Although increased endothelin-3 was associated with features suggesting a reduced effective volemia, it is likely that other mechanisms than hypovolemia were mainly responsible for high plasma endothelin levels. Increased endothelin production may play a role in circulatory and renal function abnormalities of advanced cirrhosis.

Adult↗

Hemodynamic and renal effects of ascites apheresis, concentration and reinfusion in advanced cirrhosis.

BACKGROUND/AIMS: We studied the effects of ascites apheresis, concentration and reinfusion, a new form of treatment for tense or refractory ascites, on systemic hemodynamics and renal function. METHODS: Twelve patients with advanced cirrhosis (two belonging to Child-Pugh's class B and the remainder to class C) were monitored. They were evaluated under baseline conditions, just after the treatment, and 24 and 48 h after baseline assessment. In addition to systemic hemodynamics--as evaluated by Doppler echocardiography--and renal function, indirect markers of effective volemia, such as atrial natriuretic factor, plasma renin activity and aldosterone concentration, and plasma norepinephrine were also measured. RESULTS: The technique led to significant changes in systemic hemodynamics, such as an increase in stroke volume and cardiac output. However, due to a striking reduction in peripheral vascular resistance, mean arterial pressure also declined. The hemodynamic changes were associated with a parallel increase in atrial natriuretic factor. Despite the reduction in arterial pressure, plasma renin activity also significantly declined, while plasma norepinephrine did not undergo significant changes. Although an improvement in glomerular filtration rate and renal sodium excretion occurred, neither change reached statistical significance. All the hemodynamic, renal and neuro-humoral changes described above subsided almost entirely after 48 h, when no significant changes with respect to baseline values were any longer detectable with the exception of a slight reduction in mean arterial pressure. CONCLUSIONS: In advanced cirrhosis ascites apheresis, concentration and reinfusion enhance central volemia, but an exaggerated peripheral vasodilation largely wastes the potential favourable effect on arterial volemia. As a result, no significant improvement in renal perfusion and sodium excretion can ensue.

Adult↗

Hyperdynamic circulation of advanced cirrhosis: a re-appraisal based on posture-induced changes in hemodynamics.

Little is known about the effect of posture on the circulatory abnormalities of advanced cirrhosis. We evaluated the systemic hemodynamics, measured by Doppler-echocardiography, atrial natriuretic factor, plasma renin activity and plasma norepinephrine, in 10 patients with cirrhosis and ascites and 10 healthy controls, after 2 h of standing and during lying down for a further 2 h. Standing hemodynamic patterns of controls and patients with cirrhosis did not differ significantly. The latter, however, showed higher plasma renin activity, norepinephrine and atrial natriuretic factor. The assumption of the supine position led to greater increases in cardiac index and atrial natriuretic factor, and reduction in systemic vascular resistance in patients with cirrhosis. Norepinephrine and plasma renin activity declined in both groups to a similar extent, while heart rate only slowed in controls. Thus, after 2 h in the supine position, patients with cirrhosis showed hyperdynamic circulation with increased cardiac index and heart rate and reduced systemic vascular resistance. Norepinephrine, plasma renin activity and atrial natriuretic factor were also elevated. The hyperdynamic circulation in advanced cirrhosis appears during or is enhanced by lying down. This finding suggests that this syndrome is, at least in part, attributable to excessive blood volume translocation towards the central area. However, the persistent activation of renin-angiotensin and sympathoadrenergic systems suggests that a concomitant reduced vascular sensitivity to vasoconstrictors concurs in its development.

Adult↗

High plasma levels of atrial natriuretic peptide in preascitic cirrhosis: indirect evidence of reduced natriuretic effectiveness of the peptide.

Controversial results come from spot measurements of plasma atrial natriuretic peptide (ANP) in compensated cirrhotic patients. Moreover, either blunted or exaggerated natriuresis has been described after maneuvers increasing plasma ANP. This does not make it possible to delineate the ANP effectiveness. Plasma ANP, renin activity (PRA) and aldosterone and hematocrit were serially measured (7 AM, 9 AM, 6 PM, and 11 PM) in nine preascitic cirrhotic outpatients and in nine healthy subjects on normal sodium diet (150 mmol/day) and carrying on their usual activities (mobile from 7 AM to 10 PM). Daily natriuresis was monitored the day before and during the study. In both groups, ANP peaked at the end of the recumbence period (7 AM) and declined on the assumption of the upright position, so that both ANP values of the standing period were significantly lower than the mean daily level. These fluctuations were reciprocal to PRA and hematocrit changes. Patients showed steadily elevated plasma ANP and reduced PRA (ANP mean daily level: 33.3 +/- 3.8 vs. 15.5 +/- 3.2 pg/mL, P = .004; PRA: 0.76 +/- 0.23 vs. 1.66 +/- 0.21 ng/mL/hr, P = .003). Aldosterone fluctuations and mean daily level were similar in the two groups (mean daily level: 122 +/- 11 vs. 119 +/- 9 pg/mL). Natriuresis was well adapted to the sodium intake and similar in healthy subjects (day 1: 152 +/- 11 mmol; day 2: 138 +/- 12.5 mmol) and patients (143 +/- 15 mmol; 148 +/- 29 mmol). Preascitic cirrhotic patients on a normal salt intake and carrying on their usual activities develop a new steady state requiring increased ANP levels to maintain a sodium balance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of high and low pH on Ca2+i and on cell injury evoked by anoxia in perfused rat hepatocytes.

The effect of high and low pH on anoxic cell injury was studied in freshly isolated rat hepatocytes cast in agarose gel threads and perfused with Krebs-Henseleit bicarbonate buffer (KHB) saturated with 95% O2 and 5% CO2. Cytosolic free calcium (Ca2+i) was measured with aequorin, intracellular pH (pHi) with BCECF, and lactic dehydrogenase (LDH) by the increase in NADH absorbance during lactate oxidation to pyruvate. A 2 h period of anoxia was induced by perfusing the cells with KHB saturated with 95% N2 and 5% CO2. The extracellular pH (pHo) was maintained at 7.4, 6.8 or 8.0 by varying the bicarbonate concentration. The substrate was either 5 mM glucose, 15 mM glucose or 15 mM fructose. In some experiments, anoxia was performed in Ca(2+)-free media by perfusing the cells with KHB without Ca2+ but with 0.1 mM EGTA. Reducing pHo to 6.8 during anoxia did not reduce the increase in Ca2+i, but but completely abolished LDH release. Under these conditions, pHi decreased to 6.56 +/- 0.3 when glucose was the substrate and to 6.18 +/- 0.25 with 15 mM fructose. Apparently, protection against anoxic injury caused by a low pHo is associated with a low pHi but not with a reduced elevation in Ca2+i. Increasing pHo to 8.0 during anoxia increased pHi above 8.0 +/- 0.01 and doubled LDH release without significantly altering the rise in Ca2+i. When 15 mM fructose was present with a pHo of 8.0, pHi was still 8.0, but there was practically no rise in Ca2+i, and LDH release was again completely abolished. On the other hand, a Ca(2+)-free perfusate with a pHo of 8.0 kept the rise in Ca2+i below 400 nM but did not abolish the massive release of LDH caused by high pH. Since cell injury is caused by the activation of Ca(2+)-sensitive hydrolytic enzymes such as phospholipase A2, these experiments suggest that a low pH (< 6.5) prevents their activation even in the presence of a high Ca2+i. Conversely, a high pH (> 8.0) can activate hydrolytic enzymes and cause injury even in the absence of an elevated Ca2+i. The precise mechanism by which fructose protects hepatocytes against cell injury at pHi 8.0 is unclear.

Animals↗

Modular endoprosthetic replacement after total resection of the femur for malignant tumour.

Seven patients underwent total resection of the femur with replacement by the Kotz modular femur and tibia reconstruction system (KMFTR); three of these operations were for primary malignant tumours and four were salvage procedures after failed limb-sparing surgery. Clinical and radiological results were excellent or good at final follow up at an average of 23 months. A new method of radiological assessment has been used for the acetabular component of bipolar hip endoprosthesis. The polyethylene bush of the hinged knee component may wear. Reattachment of the abductors to the endoprostheses often fails and we now suture the abductors to the fascia lata. The rectus femoris muscle should be saved, if possible, after resection. When total excision of the quadriceps is indicated, the knee should be arthrodesed. The KMFTR is easy to use and has provided good medium to long term results in our cases.

Adolescent↗

Effect of vitamin E on reoxygenation injury experienced by isolated rat hepatocytes.

The pathogenic role of lipid peroxidation in the reperfusion injury of the liver is still controversial. This study was performed to determine whether the damage caused by oxygen free radicals during reoxygenation in perfused rat hepatocytes is related to lipid peroxidation. Superoxide anion was detected by lucigenin-enhanced chemiluminescence. Lipid peroxidation and cell injury were assessed by the release of malondialdehyde and lactic dehydrogenase. Upon reoxygenation following 2.5 h of anoxia, isolated hepatocytes generated considerable amount of O2-. Following O2- formation, a significant increase in malondialdehyde release was measured. Cell injury was temporally delayed relative to O2- generation, but preceded the occurrence of a significant lipid peroxidation. Treatment with Vitamin E abolished lipid peroxidation but had no effect upon superoxide anion formation and cell injury. These results suggest that in perfused rat hepatocytes non-peroxidative mechanisms are more important than peroxidative mechanisms in the pathogenesis of the early phases of reoxygenation injury.

Acridines↗

Ascites apheresis, concentration and reinfusion for the treatment of massive or refractory ascites in cirrhosis.

A new method for ascites recirculation, consisting of a cellulose diacetate filter to remove substances with molecular weight > or = 300,000, cell debris and bacteria, followed by the concentration of ascitic fluid prior to i.v. infusion, was used 24 times in 19 patients with cirrhosis and massive or refractory ascites. The amount of ascites removed was 7.67 +/- 0.49 l, which was reduced to 407 +/- 37 ml. The procedure took 367 +/- 22 min to complete. No statistically significant changes in liver function tests, coagulative parameters, platelet count or natremia were found. The activity of coagulation and fibrinolytic systems was further assessed in six patients. No changes suggesting an activation of intravascular coagulation and/or primary fibrinolysis were disclosed. An asymptomatic fall in mean arterial pressure (from 88.6 +/- 2.6 to 80.3 +/- 3.0 mmHg; p = 0.02) occurred after paracentesis and was still present 48 h after ascites reinfusion. Plasma renin activity significantly decreased at the end of the procedure, but was not associated with a proportional reduction of plasma aldosterone concentrations. Both variables returned to baseline values 48 h later. A significant increase in the glomerular filtration rate occurred just after the end of the procedure (from 50.4 +/- 9.1 to 73.1 +/- 23.5 ml/min; p < 0.05) and subsided 48 h later. In contrast, no significant changes in diuresis and renal sodium excretion were found. Complications due to volume overload and sepsis did not occur; in one case, spontaneous bacterial peritonitis developed 3 days after the procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Renal sodium handling in cirrhosis with ascites: mechanisms of impaired natriuretic response to reclining.

We recently showed that patients with compensated cirrhosis can dispose of their fluid overload while reclining. In contrast, patients with ascites fail to develop supine-induced natriuresis. To assess the effect of reclining on renal sodium handling in patients with advanced cirrhosis and the mechanisms blunting natriuresis in this situation, renal function and plasma concentrations of atrial natriuretic factor, aldosterone and norepinephrine were evaluated in 10 nonazotemic patients with cirrhosis and ascites and 10 healthy controls standing for 2 h and reclining for 2 h. While standing, all patients showed marked sodium retention and significantly elevated plasma atrial natriuretic factor levels, aldosterone and norepinephrine. Glomerular filtration rate did not differ from healthy controls. The reclining increased renal sodium excretion in both groups, but this change was far less marked in patients; natriuresis only rose to the control range in two of them. An increase in atrial natriuretic factor and a depression of plasma aldosterone and norepinephrine was seen in both controls and patients. In the latter, despite the greater change in atrial natriuretic factor and aldosterone, the aldosterone to atrial natriuretic factor ratio, which was inversely correlated with natriuresis during both standing and reclining remained significantly elevated. In the two patients who achieved normal natriuresis during reclining, reclining was associated with both the normalization of the aldosterone/atrial natriuretic factor ratio, and with an increase in glomerular filtration rate. The supine-induced increase in atrial natriuretic factor was not only preserved but was even enhanced in cirrhosis with ascites.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Oxygen free radical formation by rat hepatocytes during postanoxic reoxygenation: scavenging effect of albumin.

Free radical formation and reoxygenation injury were studied in rat hepatocytes perfused with Krebs-Henseleit bicarbonate buffer containing 1% or no albumin. After 2, 2.5, or 3 h of anoxia followed by 1 h reoxygenation in the absence of albumin, free radical formation assessed by low-level chemiluminescence and cell injury measured by lactate dehydrogenase (LDH) release and by trypan blue uptake increased proportionately. Chemiluminescence increased 4- to 7-fold, LDH release and trypan blue uptake increased 1.5- to 2-fold, compared with the end of anoxia. With 1% albumin, there was no increase in free radical formation during reoxygenation, and LDH release returned to control levels. There was a linear relation between the increase in chemiluminescence and the rise in LDH release (r2 = 0.83) and the increase in trypan blue uptake (r2 = 0.80), suggesting that free radical formation during reoxygenation is responsible for the cell injury. These experiments demonstrate that freshly isolated hepatocytes produce oxygen free radicals detectable by low-level chemiluminescence and that reoxygenation injury occurs after a relatively short period of anoxia (2-3 h). Albumin acts as a free radical scavenger, suppresses the release of reactive oxygen species, and significantly reduces reoxygenation injury.

Aerobiosis↗

Human hepatocytes are more resistant than rat hepatocytes to anoxia-reoxygenation injury.

We performed this study to determine whether perfused isolated human and rat hepatocytes have different sensitivities to anoxia-reoxygenation injury. Oxygen free radicals were detected by lucigenin-enhanced chemiluminescence. Lipid peroxidation was assessed by measuring malondialdehyde release. Cell injury was evaluated by measuring lactate dehydrogenase release and trypan blue uptake. During the control period, lucigenin-enhanced chemiluminescence, malondialdehyde and lactate dehydrogenase release and trypan blue uptake were similar in rat and human hepatocytes. During 3.5 hr of anoxia, lucigenin-enhanced chemiluminescence decreased to background levels and malondialdehyde release remained constant in both groups. In contrast, lactate dehydrogenase release increased eightfold in rat hepatocytes but only threefold in human hepatocytes. With reoxygenation after 2.5 hr of anoxia, in rat hepatocytes lucigenin-enhanced chemiluminescence increased 13-fold within 15 min and then declined toward control levels. Malondialdehyde release doubled after 1 hr of reoxygenation. The rate of lactate dehydrogenase release increased to a level almost twice that observed in cells kept continuously anoxic. In contrast, with human hepatocytes lucigenin-enhanced chemiluminescence increased only fourfold, whereas malondialdehyde and lactate dehydrogenase releases did not differ significantly from those levels measured in cells perfused continuously under anoxic conditions. At the end of the experiment, the increase in trypan blue uptake was significantly greater with rat hepatocytes than with human hepatocytes. These results demonstrate that (a) during reoxygenation following 2.5 hr of anoxia, isolated human hepatocytes generate fewer oxygen free radical, and lipoperoxides than do rat hepatocytes, and (b) human hepatocytes are more resistant to cell injury during anoxia-reoxygenation than are rat hepatocytes.

Adult↗